Obesity is a known risk factor for the development of hepatic disease; obesity-induced fatty liver can lead to inflammation, steatosis, and cirrhosis and is associated with degeneration of the mitochondria. Lifestyle interventions such as physical activity may ameliorate this condition. The purpose of this study was to investigate regulation of mitochondrial and autophagy quality control in liver following Western diet-induced obesity and voluntary physical activity. Eight-week-old C57BL/6J mice were fed a Western diet (WD) or normal chow (NC, control) for 4 weeks; afterwards, groups were divided into voluntary wheel running (VWR) or sedentary (SED) conditions for an additional 4 weeks. WD-SED animals had a median histology score of 2, whereas WD-VWR was not different from NC groups (median score 1). There was no difference in mRNA of inflammatory markers Il6 and Tnfa in WD animals. WD animals had 50% lower mitochondrial content (COX IV and Cytochrome C proteins), 50% lower Pgc1a mRNA content, and reduced content of mitochondrial fusion and fission markers. Markers of autophagy were increased in VWR animals, regardless of obesity, as measured by 50% greater LC3-II/I ratio and 40% lower p62 protein content. BNIP3 protein content was 30% less in WD animals compared with NC animals, regardless of physical activity. Diet-induced obesity results in derangements in mitochondrial quality control that appear to occur prior to the onset of hepatic inflammation. Moderate physical activity appears to enhance basal autophagy in the liver; increased autophagy may provide protection from hepatic fat accumulation.

The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.

Vegan or vegetarian diets have been suggested to reduce type 2 diabetes (T2D) risk. However, not much is known on whether variation in the degree of having a plant-based versus animal-based diet may be beneficial for prevention of T2D. We aimed to investigate whether level of adherence to a diet high in plant-based foods and low in animal-based foods is associated with insulin resistance, prediabetes, and T2D. Our analysis included 6798 participants (62.7 ± 7.8 years) from the Rotterdam Study (RS), a prospective population-based cohort in the Netherlands. Dietary intake data were collected with food-frequency questionnaires at baseline of three sub-cohorts of RS (RS-I-1: 1989-1993, RS-II-1: 2000-2001, RS-III-1: 2006-2008). We constructed a continuous plant-based dietary index (range 0-92) assessing adherence to a plant-based versus animal-based diet. Insulin resistance at baseline and follow-up was assessed using homeostasis model assessment of insulin resistance (HOMA-IR). Prediabetes and T2D were collected from general practitioners' records, pharmacies' databases, and follow-up examinations in our research center until 2012. We used multivariable linear mixed models to examine association of the index with longitudinal HOMA-IR, and multivariable Cox proportional-hazards regression models to examine associations of the index withrisk of prediabetes and T2D. During median 5.7, and 7.3 years of follow-up, we documented 928 prediabetes cases and 642 T2D cases. After adjusting for sociodemographic and lifestyle factors, a higher score on the plant-based dietary index was associated with lower insulin resistance (per 10 unitshigher score: β = -0.09; 95% CI: - 0.10; - 0.08), lower prediabetes risk (HR = 0.89; 95% CI: 0.81; 0.98), and lower T2D risk [HR = 0.82 (0.73; 0.92)]. After additional adjustment for BMI, associations attenuated and remained statistically significant for longitudinal insulin resistance [β = -0.05 (- 0.06; - 0.04)] and T2D risk [HR = 0.87 (0.79; 0.99)], but no longer for prediabetes risk [HR = 0.93 (0.85; 1.03)]. In conclusion, a more plant-based and less animal-based diet may lower risk of insulin resistance, prediabetes and T2D. These findings strengthen recent dietary recommendations to adopt a more plant-based diet.Clinical Trial Registry number and website NTR6831, http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=6831 .

There is evidence for health benefits from 'Palaeolithic' diets; however, there are a few data on the acute effects of rationally designed Palaeolithic-type meals. In the present study, we used Palaeolithic diet principles to construct meals comprising readily available ingredients: fish and a variety of plants, selected to be rich in fibre and phyto-nutrients. We investigated the acute effects of two Palaeolithic-type meals (PAL 1 and PAL 2) and a reference meal based on WHO guidelines (REF), on blood glucose control, gut hormone responses and appetite regulation. Using a randomised cross-over trial design, healthy subjects were given three meals on separate occasions. PAL2 and REF were matched for energy, protein, fat and carbohydrates; PAL1 contained more protein and energy. Plasma glucose, insulin, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and peptide YY (PYY) concentrations were measured over a period of 180 min. Satiation was assessed using electronic visual analogue scale (EVAS) scores. GLP-1 and PYY concentrations were significantly increased across 180 min for both PAL1 (P= 0·001 and P< 0·001) and PAL2 (P= 0·011 and P= 0·003) compared with the REF. Concomitant EVAS scores showed increased satiety. By contrast, GIP concentration was significantly suppressed. Positive incremental AUC over 120 min for glucose and insulin did not differ between the meals. Consumption of meals based on Palaeolithic diet principles resulted in significant increases in incretin and anorectic gut hormones and increased perceived satiety. Surprisingly, this was independent of the energy or protein content of the meal and therefore suggests potential benefits for reduced risk of obesity.

Obesity is characterized as a chronic state of low-grade inflammation with progressive immune cell infiltration into adipose tissue. Adipose tissue macrophages play a critical role in the establishment of chronic inflammatory states and metabolic dysfunctions.(.)andextract polyphenols exhibit anti-carcinogenesis, anti-inflammatory, and anti-oxidant activities. However, the action ofpolyphenols in obesity-related inflammation has not been reported. The aim of this study was to explore the anti-inflammatory action of polyphenols fromextract (ISE) in macrophages and the interaction between macrophages and adipocytes.RAW264.7 macrophages were stimulated with LPS or conditioned medium of hypertrophied 3T3-L1 adipocytes or cocultured with differentiated adipocytes in the presence of different doses of ISE. The inflammatory cytokines were evaluated by ELISA, the MAPK, NF-κB, and IL-6/STAT3 signals were determined by immunoblotting, and the migrated function of macrophages was determined by migration assay.ISE suppressed the inflammatory mediators including NO, TNF-α, IL-6, and MCP-1 induced by either LPS or conditioned medium derived from 3T3-L1 adipocytes. ISE also decreased the production of these inflammatory mediators in cocultures of 3T3-L1 adipocytes and RAW264.7 macrophages. Furthermore, ISE blocked RAW264.7 macrophages migration toward 3T3-L1 adipocytes in cocultures. Finally, this effect of ISE might be mediated via inhibiting ERK, p38, and STAT3 activation.Our findings indicate the possibility that ISE suppresses the interaction between macrophages and adipocytes, attenuates chronic inflammation in adipose tissue and improves obesity-related insulin resistance and complication, suggesting that ISE might be a valuable medicinal food effective in improving insulin resistance and metabolic syndrome.

The study was aimed to examine if oral administration of the aqueous extract of the whole plant OCIMUM SANCTUM (OS) protects against the development of insulin resistance in fructose fed rats. Male Wister rats were randomly divided into four groups of eight animals each: group-S (starch diet), group-F (fructose diet), group-F+OS (fructose diet along with OCIMUM SANCTUM extract at a dose of 200 mg/kg), group-S+OS (starch diet along with OCIMUM SANCTUM). During the experimental period of 60 days body weight, plasma glucose, insulin, and triglycerides were measured at an interval of 15 days. Insulin sensitivity was assessed at the end of experimental period by measuring glucose-insulin index, which is the product of the areas under the curve of glucose and insulin during oral glucose tolerance test. The nontoxic nature of OS was revealed by unaltered body weight, plasma glucose, insulin, and triglyceride levels in group-S+OS when compared with group-S. A significant gain in body weight, hyperglycemia, hyperinsulinemia, hypertriglyceridemia, and insulin resistance were observed in group-F when compared with group-S. OS treatment prevented the observed fructose induced alterations in group-F+OS. In conclusion, our results suggests that oral administration of OS aqueous extract could delay the development of insulin resistance in rats and may be used as an adjuvant therapy for treating diabetic patients with insulin resistance.

Breastfeeding for≥12 mo is recommended for optimal infant nutrition but may hold maternal benefits as well. Indeed, lactation has been associated with lower long-term risk of diabetes in the mother, but the mechanism by which it imparts sustained postweaning effects on glucose tolerance remains unclear. In this context, we postulated that lactation could potentially induce postweaning beneficial effects on glucose tolerance by modifying the natural history of insulin sensitivity and/or pancreatic β-cell function over time. Thus, in this study, we evaluated the relationships between duration of lactation [≤3 mo (n = 70), 3-12 mo (n = 140), and ≥12 mo (n = 120)] and trajectories of insulin sensitivity/resistance, β-cell function, and glycemia over the first 3 yr postpartum in a cohort of 330 women comprising the full spectrum of glucose tolerance in pregnancy, who underwent serial metabolic characterization, including oral glucose tolerance tests, at 3 mo, 1 yr, and 3 yr postpartum. The prevalence of dysglycemia (pre-diabetes/diabetes) at 3 yr postpartum was lower in women who breastfed for ≥12 mo (12.5%) than in those who breastfed for ≤3 mo (21.4%) or for 3-12 mo (25.7%)(overall P = 0.028). On logistic regression analysis, lactation for ≥12 mo independently predicted a lower likelihood of prediabetes/diabetes at 3 yr postpartum (OR = 0.37, 95% CI 0.18-0.78, P = 0.009). Notably, lactation for ≥12 mo predicted lesser worsening of insulin sensitivity/resistance (P<0.0001), fasting glucose (P<0.0001), and 2-h glucose (P = 0.011) over 3 yr compared with lactation≤3 mo but no differences in β-cell function (P ≥ 0.37). It has thus emerged that adherence to current breastfeeding recommendations reduces future diabetic risk through sustained postweaning effects on insulin sensitivity/resistance but not β-cell function.

BACKGROUND:Previous studies have shown that qi-gong, a form of mind-body movement therapy, may be beneficial for people with type 2 diabetes; however, no controlled studies have been conducted to examine the predictors and mediators of qi-gong effects on indicators of diabetes control. This study examined the effects of qi-gong on diabetes control and identified the predictors and mediators of these effects.

DESIGN:RCT.

SETTING/PARTICIPANTS:The study included forty-one participants (16 men and 25 women; aged 41-71 years) with elevated blood glucose levels.

INTERVENTIONS:Participants were randomized to qi-gong intervention or a usual medical care control group. Physical and hematologic measures were assessed at baseline and after 12 weeks.

MAIN OUTCOME MEASURES:The outcomes were indicators of diabetes control (HbA1c, insulin resistance, fasting blood glucose and insulin, and 2-hour blood glucose and insulin) and potential mediators of these (body weight, waist circumference, and leg strength). Data were collected in 2006 and analyzed in 2007 to 2009.

RESULTS:Linear regression analyses showed significant between-group differences in favor of the intervention group in weight (p<0.01); waist circumference (p<0.01); leg strength (p<0.01); HbA1c (p<0.05); insulin resistance (p<0.01); and fasting blood insulin (p<0.01) at 12 weeks. Logistic regression analyses showed that the qi-gong intervention was a significant predictor of reduced weight (odds for decreasing by -2 kg=11.14, p<0.01); waist circumference (by -5 cm=22.50, p<0.01); insulin resistance (by -0.2 unit=3.75, p<0.05); and improved leg strength (odds for increasing by 4 stands in 30 seconds=7.00, p<0.01). The effect of the qi-gong intervention on improved insulin resistance was mediated by reduced weight.

CONCLUSIONS:The qi-gong intervention was associated with improvements in weight, waist circumference, leg strength, and insulin resistance. The mediation analyses highlight the importance of weight reduction in the control of diabetes. TRIAL REGISTRATION #: Australian New Zealand Clinical Trials Registry: ACTRN12607000528459.

Skeletal muscle insulin resistance has been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and atherogenic dyslipidemia associated with the metabolic syndrome by altering the distribution pattern of postprandial energy storage. We conducted a study to examine this hypothesis by reversing muscle insulin resistance with a single bout of exercise and measuring hepatic de novo lipogenesis and hepatic triglyceride synthesis after a carbohydrate-rich meal. We studied 12 healthy, young, lean, insulin resistant individuals in an interventional, randomized cross-over trial. The response to the ingestion of a carbohydrate-rich meal was studied at rest and after one 45-min bout of exercise on an elliptical trainer. Hepatic de novo lipogenesis was assessed by using (2)H(2)O, and changes in glycogen and fat content in liver and muscle were measured by (13)C and (1)H magnetic resonance spectroscopy, respectively. Exercise resulted in a greater than threefold increase in postprandial net muscle glycogen synthesis (P<0.001), reflecting improved muscle insulin responsiveness, and a≈40% reduction (P<0.05) in net hepatic triglyceride synthesis. These changes in whole body energy storage were accompanied by a≈30% decrease in hepatic de novo lipogenesis (P<0.01) and were independent of changes in fasting or postprandial plasma glucose and insulin concentrations. These data demonstrate that skeletal muscle insulin resistance is an early therapeutic target for the treatment and prevention of atherogenic dyslipidemia and NAFLD in young insulin resistant individuals who are prone to develop the metabolic syndrome and type 2 diabetes.

BACKGROUND:and purpose Acupuncture has gained increasing attention in the treatment of insulin resistance (IR). This study systematically reviews the efficacy of acupuncture on clinical IR outcomes.

METHODS:Cochrane Central Register of Controlled Trials, Embase, Medline (via OVID), China National Knowledge Infrastructure (CNKI), Wan Fang and China Science and Technology Journal Database (VIP) were searched to collect randomized controlled trials (RCTs) of patients with IR treated by acupuncture. Meta-analysis was performed by RevMan 5.3.

RESULTS:With acupuncture, the homeostasis model assessment of insulin resistance (homa-IR) significantly decreased (mean difference (MD) = -1.04, 95% confidence interval (CI) -1.37 to -0.71; P < 0.00001), as did fasting blood glucose (FBG) (MD = -0.56, 95% CI -0.88 to -0.25; P = 0.0005), 2 h postprandial blood glucose (2hPG) (MD = -0.91, 95% CI -1.62 to -0.20; P = 0.01), and fasting insulin (FINS) (MD = -3.23, 95% CI -4.14 to -2; P < 0.00001). Meanwhile, the insulin sensitivity index (ISI) (MD = 0.36, 95% CI 0.18 to 0.53; P < 0.0001) increased, and fewer adverse events occurred.

CONCLUSION:Acupuncture may improve homa-IR, ISI, FBG, 2hPG and FINS with fewer adverse events than other treatments, making it a viable treatment for IR.

Exercise could afford multiple beneficial effects on obesity-related metabolic disorders. To address this issue, C57BL/6J mice were used to investigate the effects of 13 weeks of swim training on HFD-induced obesity and related insulin resistance and inflammation. Our results show that swim training can significantly prevent HFD-induced weight gain and increase resting energy expenditure without affecting food intake. The insulin sensitivity was enhanced in the HFD + swim group than in the HFD + sedentary group. Moreover, swim training considerably decreased serum LPS content and downregulates epididymis white adipose tissue (eWAT) expression of the inflammatory mediator Tnf-α, Il-6, and Mcp-1. In summary, 13 weeks of swim training could reverse HFD-induced metabolic disorders including insulin resistance and inflammation.

Chronic low-grade systemic inflammation is a feature of chronic diseases such as cardiovascular disease and type 2 diabetes. Regular exercise offers protection against all-cause mortality, primarily by protection against atherosclerosis and insulin resistance and there is evidence that physical training is effective as a treatment in patients with chronic heart diseases and type 2 diabetes. Regular exercise induces anti-inflammatory actions. During exercise, IL-6 (interleukin-6) is produced by muscle fibres. IL-6 stimulates the appearance in the circulation of other anti-inflammatory cytokines such as IL-1ra (interleukin-1 receptor antagonist) and IL-10 (interleukin-10) and inhibits the production of the pro-inflammatory cytokine TNF-alpha (tumour necrosis factor-alpha). In addition, IL-6 enhances lipid turnover, stimulating lipolysis as well as fat oxidation. It is suggested that regular exercise induces suppression of TNF-alpha and thereby offers protection against TNF-alpha-induced insulin resistance. Recently, IL-6 was introduced as the first myokine, defined as a cytokine, that is produced and released by contracting skeletal muscle fibres, exerting its effects in other organs of the body. Myokines may be involved in mediating the beneficial health effects against chronic diseases associated with low-grade inflammation such as diabetes and cardiovascular diseases.

Folk medicine stories accredited the aptitude of camel milk (CMK) as a hypoglycemic agent and recent studies have confirmed this in the diabetic patients and experimental animals. However, the mechanism(s) by which CMK influences glucose homeostasis is yet unclear. The current study investigated the changes in the glucose homeostatic parameters, the incretin hormones, and the inflammatory cytokines in the CMK-treated diabetic animals. A model of type 2 diabetes mellitus was induced in rats by intraperitoneal injection of streptozotocin 40 mg/kg/day for 4 repeated doses. Camel milk treatment was administered for 8 weeks. The changes in glucagon like peptide-1 (GLP-1), glucose dependent insulinotropic peptide (GIP), glucose tolerance, fasting and glucose-stimulated insulin secretion, insulin resistance (IR), TNF-α, TGF-β1, lipid profile, atherogenic index (AI), and body weight were investigated. The untreated diabetic animals showed hyperglycemia, increased HOMA-IR, hyperlipidemia, elevated AI, high serum incretins [GLP-1 and GIP], TNF-α, and TGF-β1 levels and weight loss as compared with the control group. Camel milk treatment to the diabetic animals resulted in significant lowered fasting glucose level, hypolipidemia, decreased HOMA-IR, recovery of insulin secretion, weight gain, and no mortality during the study. Additionally, CMK inhibits the diabetes-induced elevation in incretin hormones, TNF-α and TGF-β1 levels. The increase in glucose-stimulated insulin secretion, decreased HOMA-IR, modulation of the secretion and/or the action of incretins, and the anti-inflammatory effect are anticipated mechanisms to the antidiabetic effect of CMK and suggest it as a valuable adjuvant antidiabetic therapy.

Type 2 diabetes is a metabolic disorder that is strongly associated with cardiovascular risk. Inflammation is a potential risk factor for cardiovascular disease. In this study, hydro alcoholic extract of Nettle (Urtica dioica) on insulin sensitivity and some inflammatory indicators in type 2 diabetic patients were studied. A randomized double-blind clinical trial on 50 men and women with type 2 diabetes was done for 8 weeks. Patients were adjusted by age, sex and duration of diabetes, then randomly divided into two groups, an intervention and control group. They received, 100 mg kg-1nettle extract or placebo in three portions a day for 8 weeks. Interleukin 6 (IL-6), Tumor Necrosis Factor-alpha (TNF-alpha), High Sensitive C-Reactive protein (hs-CRP) and Fasting Insulin concentration were measured. Insulin Sensitivity was calculated, at the beginning and the end of the study. The data were analyzed by SPSS version 18, p<0.05 was considered significant for all variables. After 8 weeks, IL-6 and hs-CRP showed a significant decrease in the intervention group compared to the control group (p<0.05). The findings showed that the hydro alcoholic extract of nettle has decreasing effects on IL-6 and hs-CRP in patients with type 2 diabetes after eight weeks intervention.

Prostate cancer (PCa) is dependent on androgen receptor signaling and aberrations of the PI3K-Akt-mTORC1 pathway mediating excessive and sustained growth signaling. The nutrient-sensitive kinase mTORC1 is upregulated in nearly 100% of advanced human PCas. Oncogenic mTORC1 signaling activates key subsets of mRNAs that cooperate in distinct steps of PCa initiation and progression. Epidemiological evidence points to increased dairy protein consumption as a major dietary risk factor for the development of PCa. mTORC1 is a master regulator of protein synthesis, lipid synthesis and autophagy pathways that couple nutrient sensing to cell growth and cancer. This review provides evidence that PCa initiation and progression are promoted by cow´s milk, but not human milk, stimulation of mTORC1 signaling. Mammalian milk is presented as an endocrine signaling system, which activates mTORC1, promotes cell growth and proliferation and suppresses autophagy. Naturally, milk-mediated mTORC1 signaling is restricted only to the postnatal growth phase of mammals. However, persistent consumption of cow´s milk proteins in humans provide highly insulinotropic branched-chain amino acids (BCAAs) provided by milk´s fast hydrolysable whey proteins, which elevate postprandial plasma insulin levels, and increase hepatic IGF-1 plasma concentrationsby casein-derived amino acids. BCAAs, insulin and IGF-1 are pivotal activating signals of mTORC1. Increased cow´s milk protein-mediated mTORC1 signaling along with constant exposure to commercial cow´s milk estrogens derived from pregnant cows may explain the observed association between high dairy consumption and increased risk of PCa in Westernized societies. As well-balanced mTORC1-signaling plays an important role in appropriate prostate morphogenesis and differentiation, exaggerated mTORC1-signaling by high cow´s milk consumption predominantly during critical growth phases of prostatedevelopment and differentiation may exert long-term adverse effects on prostate health. Attenuation of mTORC1 signaling by contemporary Paleolithic diets and restriction of dairy protein intake, especially during mTORC1-dependent phases of prostate development and differentiation, may offer protection from the most common dairy-promoted cancer in men of Western societies.

PURPOSE:There is limited evidence whether environmental exposure to perfluorinated compounds (PFCs) affects insulin resistance (IR) and whether vitamin C intake protects against the adverse effect of PFCs. This study was carried out to investigate the effect of PFCs on IR through oxidative stress, and the effects of a 4-week consumption of vitamin C supplement compared placebo on development of IR by PFCs.

METHODS:For a double-blind, community-based, randomized, placebo-controlled crossover intervention of vitamin C, we assigned 141 elderly subjects to both vitamin C and placebo treatments for 4 weeks. We measured serum levels of PFCs to estimate PFC exposures and urinary levels of malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) for oxidative stress. We also measured levels of fasting glucose and insulin and derived the homeostatic model assessment (HOMA) index to assess IR.

RESULTS:Perfluorooctane sulfonate (PFOS) and perfluorododecanoic acid (PFDoDA) levels were found to be positively associated with HOMA index at the baseline and after placebo treatment. Risks of IR for the top decile of PFOS and PFDoDA exposures were significantly elevated compared with those with lower PFOS and PFDoDA exposures (both, P < 0.0001). However, the effects of PFOS and PFDoDA on HOMA disappeared after vitamin C supplementation (both, P > 0.30). Furthermore, PFOS and PFDoDA levels were also significantly associated with MDA and 8-OHdG levels, and MDA levels were positively associated with HOMA index.

CONCLUSION:PFOS and PFDoDA exposures were positively associated with IR and oxidative stress, and vitamin C supplementation protected against the adverse effects of PFOS and PFDoDA on IR.

Fibroblast growth factor-21 (FGF21) is a hormone secreted by the liver during fasting that elicits diverse aspects of the adaptive starvation response. Among its effects, FGF21 induces hepatic fatty acid oxidation and ketogenesis, increases insulin sensitivity, blocks somatic growth and causes bone loss. Here we show that transgenic overexpression of FGF21 markedly extends lifespan in mice without reducing food intake or affecting markers of NAD+ metabolism or AMP kinase and mTOR signaling. Transcriptomic analysis suggests that FGF21 acts primarily by blunting the growth hormone/insulin-like growth factor-1 signaling pathway in liver. These findings raise the possibility that FGF21 can be used to extend lifespan in other species.DOI:http://dx.doi.org/10.7554/eLife.00065.001.

BACKGROUND AND OBJECTIVES:Cognitive impairment develops with pre-diabetes and dementia is a complication of diabetes. Natural products like turmeric and cinnamon may ameliorate the underlying pathogenesis.

METHODS:People≥ 60 years (n=48) with newly-recognised untreated pre-diabetes were randomised to a double-blind metabolic study of placebo, turmeric (1 g), cinnamon (2 g) or both (1 g&2 g respectively), ingested at a white bread (119 g) breakfast. Observations were made over 6 hours for pre- and post-working memory (WM), glycaemic and insulin responses and biomarkers of Alzheimer's disease (AD)(0, 2, 4 and 6 hours): amyloid precursor protein (APP),γ-secretase subunits presenilin-1 (PS1), presenilin-2 (PS2), and glycogen synthase kinase (GSK-3β). Differences between natural product users and non-users were determined by Students t and chi square tests; and between pre-test and post-test WM by Wilcoxon signed rank tests. Interaction between turmeric and cinnamon was tested by 2-way ANOVA. Multivariable linear regression (MLR) took account of BMI, glycaemia, insulin and AD biomarkers in the WM responses to turmeric and cinnamon.

RESULTS:No interaction between turmeric and cinnamon was detected. WM increased from 2.6 to 2.9 out of 3.0 (p=0.05) with turmeric, but was unchanged with cinnamon. WM improvement was inversely associated with insulin resistance (r=-0.418, p<0.01), but not with AD biomarkers. With MLR, the WM responses to turmeric were best predicted with an R2 of 34.5%; and with significant turmeric, BMI and insulin/glucose AUC beta-coefficients.

CONCLUSIONS:Co-ingestion of turmeric with white bread increases working memory independent of body fatness, glycaemia, insulin, or AD biomarkers.

Diabet. Med. 28, 549-559 (2011) ABSTRACT: Aims  The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods  A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted(-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results  Forty-three per cent of participants in the experimental group and 5% of participants in the control groupreduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental groupthan in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions  A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet.

OBJECTIVES:A vegetarian diet may prevent elevation of blood pressures and lower the risk for hypertension through lower degrees of obesity, inflammation, and insulin resistance. This study investigated the association between a vegetarian diet and hypertension incidence in a cohort of Taiwanese adult nonsmokers and examined whether this association was mediated through inflammation, abdominal obesity, or insulin resistance (using fasting glucose as a proxy).

METHODS:This matched cohort study was from the 1994-2008 MJ Health Screening Database. Each vegetarian was matched with five nonvegetarians by age, sex, and study site. The analysis included 4109 nonsmokers (3423 nonvegetarians and 686 vegetarians), followed for a median of 1.61 years. The outcome includes hypertension incidence, as well as SBP and DBP levels. Regression analysis was performed to assess the association between vegetarian diet and hypertension incidence or future blood pressure levels in the presence/absence of potential mediators.

RESULTS:Vegetarians had a 34% lower risk for hypertension, adjusting for age and sex (odds ratio: 0.66, 95% confidence interval: 0.50-0.87; SBP: -3.3 mmHg, P < 0.001; DBP: -1.5 mmHg, P < 0.001). The results stay statistically significant after further adjustment for C-reactive protein, waist circumference, and fasting glucose (odds ratio: 0.72, 95% confidence interval: 0.55-0.86; SBP: -2.4 mmHg, P < 0.05; DBP: -1.1 mmHg, P < 0.05). The protective association between vegetarian diet and hypertension appeared to be consistent across age groups.

CONCLUSION:Taiwanese vegetarians had lower incidence of hypertension than nonvegetarians. Vegetarian diets may protect against hypertension beyond lower abdominal obesity, inflammation, and insulin resistance.